NM_020208.4:c.417T>C

Variant names:

• chr3-45775926-A-G
• rs758386
• NM_020208.4:c.417T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_020208.4(SLC6A20):​c.417T>C​(p.Cys139Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.955 in 1,614,194 control chromosomes in the GnomAD database, including 735,934 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.96 (70175 hom., cov: 32)
  • Exomes 𝑓: 0.95 (665759 hom.)
• Consequence: SLC6A20 NM_020208.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.325
• Publications: 26 publications found

Genes affected

SLC6A20 (HGNC:30927): (solute carrier family 6 member 20) Transport of small hydrophilic substances across cell membranes is mediated by substrate-specific transporter proteins which have been classified into several families of related genes. The protein encoded by this gene belongs to the sodium:neurotransmitter symporter (SNF) family and functions as a proline transporter expressed in kidney and small intestine. Mutations in this gene are associated with Hyperglycinuria and Iminoglycinuria. [provided by RefSeq, Jul 2020]

SLC6A20 Gene-Disease associations (from GenCC):

• hyperglycinuria

  Inheritance: Unknown, AR, AD Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 3-45775926-A-G is Benign according to our data. Variant chr3-45775926-A-G is described in ClinVar as Benign. ClinVar VariationId is 345420.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.325 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020208.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A20	NM_020208.4	MANE Select	c.417T>C	p.Cys139Cys	synonymous	Exon 4 of 11	NP_064593.1	Q9NP91-1
	SLC6A20	NM_001385683.1		c.417T>C	p.Cys139Cys	synonymous	Exon 4 of 11	NP_001372612.1	A0A8V8TQV4
	SLC6A20	NM_022405.4		c.417T>C	p.Cys139Cys	synonymous	Exon 4 of 10	NP_071800.1	Q9NP91-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A20	ENST00000358525.9	TSL:1 MANE Select	c.417T>C	p.Cys139Cys	synonymous	Exon 4 of 11	ENSP00000346298.4	Q9NP91-1
	SLC6A20	ENST00000353278.8	TSL:1	c.417T>C	p.Cys139Cys	synonymous	Exon 4 of 10	ENSP00000296133.5	Q9NP91-2
	SLC6A20	ENST00000962429.1		c.417T>C	p.Cys139Cys	synonymous	Exon 4 of 11	ENSP00000632488.1

Frequencies

GnomAD3 genomes AF: 0.960 AC: 146085 AN: 152196 Hom.: 70128 Cov.: 32

Gnomad AFR AF: 0.970

Gnomad AMI AF: 0.916

Gnomad AMR AF: 0.971

Gnomad ASJ AF: 0.978

Gnomad EAS AF: 0.917

Gnomad SAS AF: 0.951

Gnomad FIN AF: 0.948

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.957

Gnomad OTH AF: 0.957

GnomAD2 exomes AF: 0.957 AC: 240558 AN: 251454 AF XY: 0.957

Gnomad AFR exome AF: 0.971

Gnomad AMR exome AF: 0.965

Gnomad ASJ exome AF: 0.984

Gnomad EAS exome AF: 0.913

Gnomad FIN exome AF: 0.951

Gnomad NFE exome AF: 0.958

Gnomad OTH exome AF: 0.963

GnomAD4 exome AF: 0.954 AC: 1395051 AN: 1461880 Hom.: 665759 Cov.: 76 AF XY: 0.954 AC XY: 694097 AN XY: 727244

African (AFR) AF: 0.969 AC: 32436 AN: 33480

American (AMR) AF: 0.964 AC: 43114 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.982 AC: 25670 AN: 26134

East Asian (EAS) AF: 0.918 AC: 36464 AN: 39700

South Asian (SAS) AF: 0.957 AC: 82550 AN: 86256

European-Finnish (FIN) AF: 0.951 AC: 50800 AN: 53418

Middle Eastern (MID) AF: 0.978 AC: 5642 AN: 5768

European-Non Finnish (NFE) AF: 0.954 AC: 1060727 AN: 1112004

Other (OTH) AF: 0.955 AC: 57648 AN: 60396

GnomAD4 genome AF: 0.960 AC: 146191 AN: 152314 Hom.: 70175 Cov.: 32 AF XY: 0.960 AC XY: 71487 AN XY: 74482

African (AFR) AF: 0.970 AC: 40282 AN: 41548

American (AMR) AF: 0.971 AC: 14861 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.978 AC: 3397 AN: 3472

East Asian (EAS) AF: 0.917 AC: 4750 AN: 5178

South Asian (SAS) AF: 0.951 AC: 4590 AN: 4824

European-Finnish (FIN) AF: 0.948 AC: 10073 AN: 10626

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.957 AC: 65088 AN: 68038

Other (OTH) AF: 0.958 AC: 2025 AN: 2114

Alfa AF: 0.958 Hom.: 314386

Bravo AF: 0.961

Asia WGS AF: 0.919 AC: 3197 AN: 3478

EpiCase AF: 0.958

EpiControl AF: 0.961

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Hyperglycinuria (2)
-	-	2	not provided (2)
-	-	1	SLC6A20-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.34
DANN	Benign	0.46
PhyloP100		-0.33
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs758386; hg19: chr3-45817418; COSMIC: COSV108191667; COSMIC: COSV108191667;